Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Jul;92(1):54–61. doi: 10.1172/JCI116599

Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis.

T Abe 1, K Okamura 1, M Ono 1, K Kohno 1, T Mori 1, S Hori 1, M Kuwano 1
PMCID: PMC293529  PMID: 7686924

Abstract

We have developed two different models of tumor angiogenesis by human brain tumors: one being tube formation by bovine aortic endothelial (BAE) cells cocultured with tumor cells in vitro, and other being in vivo angiogenesis in mice when tumor cells are transplanted into the dorsal sac. We investigated whether tube formation could be induced in BAE cells in type I collagen gel when these cells were cocultured with seven human glioma cell lines. Four of the seven glioma cell lines, which had high levels of basic fibroblast growth factor (bFGF) mRNA, induced tube formation by BAE cells. The tube formation was blocked by coadministration of anti-bFGF antibody. In in vivo model system of tumor angiogenesis in mice, these four cell lines were highly angiogenic. In contrast, with the other three glioma cell lines, which had poor expression of bFGF, BAE cells showed no apparent tube formation. These three cell lines did not efficiently develop capillary networks in mice. The results demonstrated a correlative relationship in the tubulogenesis of BAE cells, bFGF mRNA levels and angiogenesis in mice. The present study with two model systems of tumor angiogenesis suggests that the angiogenesis of some human glioma cell lines is mediated by bFGF, possibly via paracrine control.

Full text

PDF
54

Images in this article

56Image
on p.56
57Image
on p.57
58Image
on p.58
58Image
on p.58
58Image
on p.58
58Image
on p.58
59Image
on p.59

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Crum R., Szabo S., Folkman J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science. 1985 Dec 20;230(4732):1375–1378. doi: 10.1126/science.2416056. [DOI] [PubMed] [Google Scholar]
  2. D'Amore P. A. Modes of FGF release in vivo and in vitro. Cancer Metastasis Rev. 1990 Nov;9(3):227–238. doi: 10.1007/BF00046362. [DOI] [PubMed] [Google Scholar]
  3. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  4. Derynck R. Transforming growth factor alpha. Cell. 1988 Aug 26;54(5):593–595. doi: 10.1016/s0092-8674(88)80001-1. [DOI] [PubMed] [Google Scholar]
  5. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  6. Folkman J., Watson K., Ingber D., Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature. 1989 May 4;339(6219):58–61. doi: 10.1038/339058a0. [DOI] [PubMed] [Google Scholar]
  7. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4–6. doi: 10.1093/jnci/82.1.4. [DOI] [PubMed] [Google Scholar]
  8. Gospodarowicz D., Bialecki H., Thakral T. K. The angiogenic activity of the fibroblast and epidermal growth factor. Exp Eye Res. 1979 May;28(5):501–514. doi: 10.1016/0014-4835(79)90038-1. [DOI] [PubMed] [Google Scholar]
  9. Gospodarowicz D., Massoglia S., Cheng J., Lui G. M., Böhlen P. Isolation of pituitary fibroblast growth factor by fast protein liquid chromatography (FPLC): partial chemical and biological characterization. J Cell Physiol. 1985 Feb;122(2):323–332. doi: 10.1002/jcp.1041220223. [DOI] [PubMed] [Google Scholar]
  10. Gospodarowicz D., Neufeld G., Schweigerer L. Fibroblast growth factor: structural and biological properties. J Cell Physiol Suppl. 1987;Suppl 5:15–26. doi: 10.1002/jcp.1041330405. [DOI] [PubMed] [Google Scholar]
  11. Gospodarowicz D., Neufeld G., Schweigerer L. Molecular and biological characterization of fibroblast growth factor, an angiogenic factor which also controls the proliferation and differentiation of mesoderm and neuroectoderm derived cells. Cell Differ. 1986 Jul;19(1):1–17. doi: 10.1016/0045-6039(86)90021-7. [DOI] [PubMed] [Google Scholar]
  12. Hamanaka R., Kohno K., Seguchi T., Okamura K., Morimoto A., Ono M., Ogata J., Kuwano M. Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. J Biol Chem. 1992 Jul 5;267(19):13160–13165. [PubMed] [Google Scholar]
  13. Kandel J., Bossy-Wetzel E., Radvanyi F., Klagsbrun M., Folkman J., Hanahan D. Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell. 1991 Sep 20;66(6):1095–1104. doi: 10.1016/0092-8674(91)90033-u. [DOI] [PubMed] [Google Scholar]
  14. Lee P. L., Johnson D. E., Cousens L. S., Fried V. A., Williams L. T. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science. 1989 Jul 7;245(4913):57–60. doi: 10.1126/science.2544996. [DOI] [PubMed] [Google Scholar]
  15. Maciag T., Mehlman T., Friesel R., Schreiber A. B. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. Science. 1984 Aug 31;225(4665):932–935. doi: 10.1126/science.6382607. [DOI] [PubMed] [Google Scholar]
  16. Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol. 1990;6:597–641. doi: 10.1146/annurev.cb.06.110190.003121. [DOI] [PubMed] [Google Scholar]
  17. Matsuda T., Okamura K., Sato Y., Morimoto A., Ono M., Kohno K., Kuwano M. Decreased response to epidermal growth factor during cellular senescence in cultured human microvascular endothelial cells. J Cell Physiol. 1992 Mar;150(3):510–516. doi: 10.1002/jcp.1041500311. [DOI] [PubMed] [Google Scholar]
  18. Mawatari M., Kohno K., Mizoguchi H., Matsuda T., Asoh K., Van Damme J., Welgus H. G., Kuwano M. Effects of tumor necrosis factor and epidermal growth factor on cell morphology, cell surface receptors, and the production of tissue inhibitor of metalloproteinases and IL-6 in human microvascular endothelial cells. J Immunol. 1989 Sep 1;143(5):1619–1627. [PubMed] [Google Scholar]
  19. Mawatari M., Okamura K., Matsuda T., Hamanaka R., Mizoguchi H., Higashio K., Kohno K., Kuwano M. Tumor necrosis factor and epidermal growth factor modulate migration of human microvascular endothelial cells and production of tissue-type plasminogen activator and its inhibitor. Exp Cell Res. 1991 Feb;192(2):574–580. doi: 10.1016/0014-4827(91)90078-9. [DOI] [PubMed] [Google Scholar]
  20. Montesano R., Vassalli J. D., Baird A., Guillemin R., Orci L. Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7297–7301. doi: 10.1073/pnas.83.19.7297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morimoto A., Okamura K., Hamanaka R., Sato Y., Shima N., Higashio K., Kuwano M. Hepatocyte growth factor modulates migration and proliferation of human microvascular endothelial cells in culture. Biochem Biophys Res Commun. 1991 Sep 16;179(2):1042–1049. doi: 10.1016/0006-291x(91)91924-2. [DOI] [PubMed] [Google Scholar]
  22. Moscatelli D. High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells. J Cell Physiol. 1987 Apr;131(1):123–130. doi: 10.1002/jcp.1041310118. [DOI] [PubMed] [Google Scholar]
  23. Moses H. L., Yang E. Y., Pietenpol J. A. TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. Cell. 1990 Oct 19;63(2):245–247. doi: 10.1016/0092-8674(90)90155-8. [DOI] [PubMed] [Google Scholar]
  24. Murphy P. R., Sato R., Sato Y., Friesen H. G. Fibroblast growth factor messenger ribonucleic acid expression in a human astrocytoma cell line: regulation by serum and cell density. Mol Endocrinol. 1988 Jul;2(7):591–598. doi: 10.1210/mend-2-7-591. [DOI] [PubMed] [Google Scholar]
  25. Neufeld G., Gospodarowicz D. Protamine sulfate inhibits mitogenic activities of the extracellular matrix and fibroblast growth factor, but potentiates that of epidermal growth factor. J Cell Physiol. 1987 Aug;132(2):287–294. doi: 10.1002/jcp.1041320213. [DOI] [PubMed] [Google Scholar]
  26. Okamura K., Morimoto A., Hamanaka R., Ono M., Kohno K., Uchida Y., Kuwano M. A model system for tumor angiogenesis: involvement of transforming growth factor-alpha in tube formation of human microvascular endothelial cells induced by esophageal cancer cells. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1471–1479. doi: 10.1016/s0006-291x(05)81572-4. [DOI] [PubMed] [Google Scholar]
  27. Okamura K., Sato Y., Matsuda T., Hamanaka R., Ono M., Kohno K., Kuwano M. Endogenous basic fibroblast growth factor-dependent induction of collagenase and interleukin-6 in tumor necrosis factor-treated human microvascular endothelial cells. J Biol Chem. 1991 Oct 15;266(29):19162–19165. [PubMed] [Google Scholar]
  28. Ono M., Okamura K., Nakayama Y., Tomita M., Sato Y., Komatsu Y., Kuwano M. Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha. Biochem Biophys Res Commun. 1992 Dec 15;189(2):601–609. doi: 10.1016/0006-291x(92)92243-q. [DOI] [PubMed] [Google Scholar]
  29. Pepper M. S., Belin D., Montesano R., Orci L., Vassalli J. D. Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro. J Cell Biol. 1990 Aug;111(2):743–755. doi: 10.1083/jcb.111.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Polverini P. J., Leibovich S. J. Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Invest. 1984 Dec;51(6):635–642. [PubMed] [Google Scholar]
  31. Presta M., Moscatelli D., Joseph-Silverstein J., Rifkin D. B. Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration. Mol Cell Biol. 1986 Nov;6(11):4060–4066. doi: 10.1128/mcb.6.11.4060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rastinejad F., Polverini P. J., Bouck N. P. Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell. 1989 Feb 10;56(3):345–355. doi: 10.1016/0092-8674(89)90238-9. [DOI] [PubMed] [Google Scholar]
  33. Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Roberts A. B., Anzano M. A., Wakefield L. M., Roche N. S., Stern D. F., Sporn M. B. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. doi: 10.1073/pnas.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Saksela O., Moscatelli D., Rifkin D. B. The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells. J Cell Biol. 1987 Aug;105(2):957–963. doi: 10.1083/jcb.105.2.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sato Y., Okamura K., Morimoto A., Hamanaka R., Hamaguchi K., Shimada T., Ono M., Kohno K., Sakata T., Kuwano M. Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro. Exp Cell Res. 1993 Feb;204(2):223–229. doi: 10.1006/excr.1993.1028. [DOI] [PubMed] [Google Scholar]
  37. Sato Y., Rifkin D. B. Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis. J Cell Biol. 1988 Sep;107(3):1199–1205. doi: 10.1083/jcb.107.3.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sato Y., Rifkin D. B. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol. 1989 Jul;109(1):309–315. doi: 10.1083/jcb.109.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schreiber A. B., Winkler M. E., Derynck R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science. 1986 Jun 6;232(4755):1250–1253. doi: 10.1126/science.2422759. [DOI] [PubMed] [Google Scholar]
  40. Schweigerer L., Neufeld G., Friedman J., Abraham J. A., Fiddes J. C., Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987 Jan 15;325(6101):257–259. doi: 10.1038/325257a0. [DOI] [PubMed] [Google Scholar]
  41. Schweigerer L., Neufeld G., Friedman J., Abraham J. A., Fiddes J. C., Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987 Jan 15;325(6101):257–259. doi: 10.1038/325257a0. [DOI] [PubMed] [Google Scholar]
  42. Sommer A., Brewer M. T., Thompson R. C., Moscatelli D., Presta M., Rifkin D. B. A form of human basic fibroblast growth factor with an extended amino terminus. Biochem Biophys Res Commun. 1987 Apr 29;144(2):543–550. doi: 10.1016/s0006-291x(87)80001-3. [DOI] [PubMed] [Google Scholar]
  43. Stefanik D. F., Rizkalla L. R., Soi A., Goldblatt S. A., Rizkalla W. M. Acidic and basic fibroblast growth factors are present in glioblastoma multiforme. Cancer Res. 1991 Oct 15;51(20):5760–5765. [PubMed] [Google Scholar]
  44. Takahashi J. A., Fukumoto M., Kozai Y., Ito N., Oda Y., Kikuchi H., Hatanaka M. Inhibition of cell growth and tumorigenesis of human glioblastoma cells by a neutralizing antibody against human basic fibroblast growth factor. FEBS Lett. 1991 Aug 19;288(1-2):65–71. doi: 10.1016/0014-5793(91)81004-r. [DOI] [PubMed] [Google Scholar]
  45. Takahashi J. A., Mori H., Fukumoto M., Igarashi K., Jaye M., Oda Y., Kikuchi H., Hatanaka M. Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5710–5714. doi: 10.1073/pnas.87.15.5710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zagzag D., Miller D. C., Sato Y., Rifkin D. B., Burstein D. E. Immunohistochemical localization of basic fibroblast growth factor in astrocytomas. Cancer Res. 1990 Nov 15;50(22):7393–7398. [PubMed] [Google Scholar]
  47. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES